文档介绍：该【NDA-22-291---FDA市公开课一等奖课件名师大赛获奖课件 】是由【可爱的嘎GD】上传分享，文档一共【43】页，该文档可以免费在线阅读，需要了解更多关于【NDA-22-291---FDA市公开课一等奖课件名师大赛获奖课件 】的内容，可以使用淘豆网的站内搜索功能，选择自己适合的文档，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此文档到您的设备，方便您编辑和打印。NDA22-291PROMACTA?(Eltrombopag)FDAReviewAndrewDmytrijuk,MD1ProposedIndicationEltrombopagisindicatedfortheshort-termtreatmentofpreviously-treatedpatientswithchronicidiopathicthrombocytopenicpurpura(ITP),administereddailyBindstotransmembraneportionofTPO receptorPreclinicaltestingofEltrombopag:stimulatedplateletsonlyinchimpanzeesinotheranimals(inhighdoses):ChronicprogressivenephropathyLiverabnormalitiesCataractsPreclinicaltestingofanotherTPO receptoragonist:marrowfibrosis3ClinicalDatabase Eltrombopag(E)exposuren=1088ChronicITP:n=330ThrombocytopeniainhepatitisC:n=56Chemotherapy-inducedthrombocytopenia:n=134Clinicalpharmacology:N=5684ITPProgram“Shortterm”:6weekexposure-Completed:placebocontrolled -773A -773B-On-going,singlearm:“REPEAT” “Longterm”:≥6monthexposure-On-going:placebocontrolled:“RAISE”-On-going:singlearm:“EXTEND”5MajorReviewTopics:“ShortTerm”Efficacy:increaseplateletcountsreduceorpreventbleedingSafety:bleedingrisksfollowingdrugdiscontinuationhepatotoxicity“shortterm”indicationbutlongtermusage -morehepatotoxicity? -potentialmarrowfibrosis?6DataPresentationCompletedstudies(short-term):773A773BOn-goingstudies/interim:REPEAT(cyclesofshort-term)EXTENDRAISE7“ShortTerm”Rationale: Protocols“ShorttermtreatmentmayincreaseplateletcountsinpatientswithchronicITPscheduledforsurgicalordentalprocedures,wherealowplateletcountcanbeahindranceorevenprohibitiveoftheprocedureduetotheriskofexcessivebleeding.”Underlinesaddedforemphasis8Studies773Aand773B:DesignFeaturesDB,PC,multi-nationalEligibility:-platelets<30Kdespiteatleast1priortherapy-didnotselectpatientsscheduledforproceduresRandomization:-773A:placebooractivedrugat 30mg,50mgor75mgdaily-773B:placebooractivedrugat50mgdaily9773Aand773B:DesignFeatures,continuedDoseadjustment:-dosingterminatedforPltct>200K-773B:couldincreasedoseto75mgatday22Majorbaselineandfollow-upevaluations:-CBC,clinicalchemistry-WHObleedingscoreEndpoints:-Primary:Pltct≥50Katday43ordrugd/c duetoPltct>200K(“response”)-Other:changeinWHObleedingscore10